Malignant glaucoma treated by low-dose laser cycloplasty: a 1-year multicenter prospective noncomparative study

AIM:To report a one-year clinical outcomes of low-dose laser cycloplasty(LCP)among malignant glaucoma patients.METHODS:In this prospective,multicenter,noncomparative clinical study,participants with malignant glaucoma were recruited and underwent LCP at eight ophthalmic centers in China.Patients were followed up at 1wk,1,3,6,and 12mo.Intraocular pressure(IOP),number of glaucoma medications,anterior chamber depth(ACD),and complications were recorded.Anatomical success was defined as the reformation of the anterior chamber based on slit-lamp biomicroscopy.Recurrence was defined by the presence of a shallow orflat anterior chamber after initial recovery from treatment.RESULTS:A total of 34 eyes received LCP.Mean IOP and medications decreased from 36.1±11.5 mm Hg with 3.3±1.5 glaucoma medications pre-treatment to 20.9±9.8 mm Hg(P<0.001)with 2.9±1.6 medications(P=0.046)at 1d,and 17.4±6.7 mm Hg(P<0.001)with 1.3±1.7 medications(P<0.001)at 12mo.The ACD increased from 1.1±0.8 mm at baseline to 1.7±1.0 mm and to 2.0±0.5 mm at 1d and 12mo,respectively.A total of 32(94.1%)eyes achieved initial anatomical success.During follow-up,2(5.9%)eyes failed and 8(23.5%)eyes relapsed,yielding a 12-month anatomical success rate of 64.3%.Complications including anterior synechia(8.82%),choroidal/ciliary detachment(5.88%)and hypopyon(2.94%)were observed within 1wk.CONCLUSION:LCP is simple,safe,and effective in reforming the anterior chamber in malignant glaucoma.

Oral fruquintinib combined with tegafur-gimeracil-oteracil potassium for advanced colorectal cancer to obtain longer progression-free survival:A case report

BACKGROUND After the failure of second-line standard therapy,effective treatment options for metastatic colorectal cancer are limited,and the duration of remission cannot meet clinical needs.In addition,associated drug toxicity may lead to treatment interruption that may affect patient outcomes.Therefore,more safe,effective and convenient treatments are urgently needed.CASE SUMMARY Here,we describe a patient with advanced colorectal cancer with multiple metastases in both lungs.Oxaliplatin combined with 5-fluorouracil or capecitabine was given as the first-line treatment,and bevacizumab combined with irinotecan was given as the second-line treatment after disease progression.However,treatment was interrupted due to recurrent grade 2 nausea and grade 1 diarrhea.He received targeted therapy with fruquintinib starting on August 26,2020 and responded well for 12 mo.After slow progression of the lung metastases,progression-free survival was again achieved over 13.5 mo by continued treatment of fruquintinib in combination with tegafur-gimeracil-oteracil potassium chemotherapy.Overall treatment duration was more than 25.5 mo.The treatments delayed tumor progression,reduced drug side effects,maintained a good quality of life,and further extended overall survival.CONCLUSION This case report detailed preliminary evidence showing that the combination of fruquintinib with tegafur-gimeracil-oteracil potassium chemotherapy double oral therapy may result in longer progression-free survival in patients with advanced colorectal cancer.

Preliminary study on the efficacy of lacrimal duct reconstruction with pedicled conjunctival flap in the treatment of severe lacrimal canalicular obstruction with conjunctivochalasis

AIM:To determine the efficacy and safety of pedicled conjunctival lacrimal duct reconstruction in the treatment of severe obstruction of superior and inferior lacrimal canaliculi with conjunctivochalasis.METHODS:This study was per formed as a retrospective analysis of patients who received conjunctival dacryocystorhinostomy with pedicled conjunctival flap reconstruction combined with tube intubation due to severe superior and inferior lacrimal canalicular obstruction with conjunctivochalasis from January 2019 to October 2019.The clinical data included the degree of preoperative epiphora and postoperative relief,preoperative examination of lacrimal duct computed tomography and ultrasound biomicroscopy,postoperative evaluation of lacrimal duct function by chloramphenicol taste and fluorescein dye disappearance test,etc.Syringing was carried out to determine the reconstruction and patency of the lacrimal duct.RESULTS:All 9 patients(9 eyes)had severe canalicular obstruction with conjunctivochalasis.The patients included 4 males and 5 females aged between 47–65y with an average age of 52.2±6.7y.At 3mo follow-up,the tube was removed and the patients were followed for a further 3mo.After tube removal,6 patients showed no epiphora.These patients also had positive chloramphenicol tastes and normal fluorescein dye disappearance test results.Two patientshad epiphora.Also,syringing showed partial patency of the reconstructed lacrimal duct.One patient had no improvement in epiphora with negative chloramphenicol taste and fluorescein dye disappearance test results and obstruction of the reconstructed lacrimal duct.The total effective rate of the operation was 8/9,with no serious complications.CONCLUSION:Pedicled conjunctival lacrimal duct reconstruction conjunctival dacryocystorhinostomy is safe and effective for superior and inferior canalicular obstruction with conjunctivochalasis.

Osteopontin promotes gastric cancer progression via phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway

BACKGROUND Gastric cancer(GC)is one of the most common malignant tumors.Osteopontin(OPN)is thought to be closely related to the occurrence,metastasis and prognosis of many types of tumors.AIM To investigate the effects of OPN on the proliferation,invasion and migration of GC cells and its possible mechanism.METHODS The mRNA and protein expression of OPN in the GC cells were analyzed by realtime quantitative-reverse transcription polymerase chain reaction and western blotting,and observe the effect of varying degree expression OPN on the proliferation and other behaviors of GC.Next,the effects of OPN knockdown on GC cells migration and invasion were examined.The short hairpin RNA(shRNA)and negative control shRNA targeting OPN-shRNA were transfected into the cells according to the manufacturer’s instructions.Non transfected cells were classified as control in the identical transfecting process.24 h after RNA transfection cell proliferation activity was detected by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide assay,and cell invasiveness and migration were detected by Trans well assay.Meanwhile,the expression of protein kinase B(AKT),matrix metalloproteinase 2(MMP-2)and vascular endothelial growth factor(VEGF)in the human GC cell lines was detected by reverse transcription polymerase chain reaction and western blotting.RESULTS The results of this study revealed that OPN mRNA and protein expression levels were highly expressed in SGC-7901 cells.OPN knockdown by specific shRNA noticeably reduced the capabilities of proliferation,invasion and migration of SGC-7901 cells.Moreover,in the experiments of investigating the underlying mechanism,results showed that OPN knockdown could down-regulated the expression of MMP-2 and VEGF,it also decreased the phosphorylation of AKT.Meanwhile,the protein expression levels of MMP-2,VEGF and phosphorylated AKT was noticeable lower than that in control group in the GC cells after they were added to phosphatidylinositol-3-kinase(PI3K)inhibitor(LY294002).CONCLUSION These results suggested that OPN though PI3K/AKT/mammalian target of rapamycin signal pathway to upregulate MMP-2 and VEGF expression,which contribute SGC-7901 cells to proliferation,invasion and migration.Thus,our results demonstrate that OPN may serve as a novel prognostic biomarkers as well as a potential therapeutic targets for GC.

Therapeutic effects of the TST36 stapler on rectocele combined with internal rectal prolapse

BACKGROUND The most common causes of outlet obstructive constipation(OOC)are rectocele and internal rectal prolapse.The surgical methods for OOC are diverse and difficult,and the postoperative complications and recurrence rate are high,which results in both physical and mental pain in patients.With the continuous deepening of the surgeon’s concept of minimally invasive surgery and continuous in-depth research on the mechanism of OOC,the treatment concepts and surgical methods are continuously improved.AIM To determine the efficacy of the TST36 stapler in the treatment of rectocele combined with internal rectal prolapse.METHODS From January 2017 to July 2019,49 female patients with rectocele and internal rectal prolapse who met the inclusion criteria were selected for treatment using the TST36 stapler.RESULTS Forty-five patients were cured,4 patients improved,and the cure rate was 92%.The postoperative obstructed defecation syndrome score,the defecation frequency score,time/straining intensity,and sensation of incomplete evacuation were significantly decreased compared with these parameters before treatment,and the differences were statistically significant(P<0.05).The postoperative anal canal resting pressure and maximum squeeze pressure in patients decreased compared with before treatment,and the differences were statistically significant(P<0.05).The initial and maximum defecation thresholds after surgery were significantly lower than those before treatment,and the differences were statistically significant(P<0.05).The postoperative ratings of rectocele,resting phase,and defecation phase in these patients were significantly decreased compared with those before treatment,and the differences were statistically significant(P<0.05).CONCLUSION The TST36 stapler is safe and effective in treating rectocele combined with internal rectal prolapse and is worth promoting in clinical work.

EXPRESSION AND SIGNIFICANCE OF ERK PROTEIN IN HUMAN BREAST CARCINOMA

Objective: To investigate the expression of ERK and p-ERK protein in human breast cancer and their corresponding tissue, to assess the significance of ERK signal pathway in tumorigenesis and progression of breast carcinoma. Methods: 40 breast cancer cases were used in S-P immunohistochemistry technique and Western Blot study. Results: The expression of ERK1, ERK2, and p- ERK protein levels increased remarkably in breast cancer tissues in comparison to normal tissues (P<0.01). The expression was upregulated by 1.32-, 1.53-and 4.27-fold, respectively. The overexpressions of ERK1, ERK2, and p- ERK proteins were obviously correlated with clinical stage of breast cancer. Protein levels of ERK and p-ERK were higher in stage III patients than in stage I and stage II patients (P<0.05). These proteins were strongly related with axillary lymph node metastasis of breast cancer, but not correlated with histopathological type and status of ER and PR of breast cancer. Expression of ERK1, and ERK2, protein showed a positive linear correlation. Conclusion: ERK signal transduction pathway is a key factor during human breast tumorigenesis and breast cancer progression.

Recovery from a biliary stricture of a common bile duct ligature injury:A case report

BACKGROUND Cholecystectomy is a common elective procedure for cholecystic diseases,including cholecystitis and cholelithiasis.Common bile duct injury is a major complication in both open and laparoscopic cholecystectomy(LC).The number of cholecystectomies performed has increased due to popularization and application of the laparoscopic technique,which has led to an increase in the number of bile duct injuries.CASE SUMMARY A 65-year-old man presented to the General Surgery Department with a complaint of repeated right upper quadrant pain for 2 years that had worsened over the previous day.The patient had a history of gallstones and hypertension.A LC was performed;it was found that a biliary stricture of 53 h duration was caused by a ligature injury of the common bile duct during the LC.Another laparoscopic exploration was performed,and the stricture was released.CONCLUSION LC is a common surgical procedure,but if a complication occurs,it is important for the surgeon to consider another exploratory surgery.

Graft rejection after deep anterior lamellar keratoplasty in fellow eye in macular corneal dystrophy: a case report

Because of the low incidence of immunological rejection,deep anterior lamellar keratoplasty(DALK)is currently the preferred treatment for macular corneal dystrophy(MCD).However,there were few reports about whether the consistent results were obtained when performing DALK in both eyes for MCD,especially when the corneal grafts were taken from different donors.Also,there were few reports about whether the stromal graft rejection occurred typically in both eyes in MCD with DALK.This case may represent the first report of an unusual and misleading manifestation of stromal graft rejection after uneventful DALK with big bubble technique in the fellow eye in MCD.A 32-year-old healthy man with MCD underwent bilateral uneventful DALK with a big bubble technique in the left eye in January and the right eye in July,the corneal grafts were taken from different donors.There was an atypical allograft rejection that occurred in the right eye and none in the left eye;although a timely diagnosis of graft rejection revealed following aqueous determination,it could not be reversed and underwent PK finally.The purpose of this case report is to illustrate the identification of atypical allograft rejection after DALK in the fellow eye,the significance of aqueous detection in the diagnosis of graft rejection,the choosing of grafts,and the timing of bilateral corneal transplantation in patients with MCD.

Therapeutic strategies targeting the epidermal growth factor receptor signaling pathway in metastatic colorectal cancer

More than 1.9 million new colorectal cancer(CRC)cases and 935000 deaths were estimated to occur worldwide in 2020,representing about one in ten cancer cases and deaths.Overall,colorectal ranks third in incidence,but second in mortality.More than half of the patients are in advanced stages at diagnosis.Treatment options are complex because of the heterogeneity of the patient population,including different molecular subtypes.Treatments have included conventional fluorouracil-based chemotherapy,targeted therapy,immunotherapy,etc.In recent years,with the development of genetic testing technology,more and more targeted drugs have been applied to the treatment of CRC,which has further prolonged the survival of metastatic CRC patients.

Digital light processing 3D printing for microfluidic chips with enhanced resolution via dosing-and zoning-controlled vat photopolymerization

Conventional manufacturing techniques to fabricate microfluidic chips,such as soft lithography and hot embossing process,have limitations that include difficulty in preparing multiple-layered structures,cost-and labor-consuming fabrication process,and low productivity.Digital light processing(DLP)technology has recently emerged as a costefficient microfabrication approach for the 3D printing of microfluidic chips;however,the fabrication resolution for microchannels is still limited to sub-100 microns at best.Here,we developed an innovative DLP printing strategy for high resolution and scalable microchannel fabrication by dosing-and zoning-controlled vat photopolymerization(DZC-VPP).Specifically,we proposed a modified mathematical model to precisely predict the accumulated UV irradiance for resin photopolymerization,thereby providing guidance for the fabrication of microchannels with enhanced resolution.By fine-tuning the printing parameters,including optical irradiance,exposure time,projection region,and step distance,we can precisely tailor the penetration irradiance stemming from the photopolymerization of the neighboring resin layers,thereby preventing channel blockage due to UV overexposure or compromised bonding stability owing to insufficient resin curing.Remarkably,this strategy can allow the preparation of microchannels with cross-sectional dimensions of 20μm×20μm using a commercial printer with a pixel size of 10μm×10μm;this is significantly higher resolution than previous reports.In addition,this method can enable the scalable and biocompatible fabrication of microfluidic drop-maker units that can be used for cell encapsulation.In general,the current DZC-VPP method can enable major advances in precise and scalable microchannel fabrication and represents a significant step forward for widespread applications of microfluidics-based techniques in biomedical fields.

Speech Recognition for Parkinson’s Disease Based on Improved Genetic Algorithm and Data Enhancement Technology

Parkinson’s disease is one of the most destructive diseases to the nervous system.Speech disorder is one of the typical symptoms of Parkinson’s disease.Approximately 90%of Parkin-son’s patients develop some degree of speech disorder,which affects speech function faster than any other subsystem of the body.Screening Parkinson’s disease by sound is a very effective method that has attracted a growing number of researchers over the past decade.Patients with Parkinson’s disease could be identified by recording the sound signal of the pronunciation of words,extracting appropriate features and identifying the disturbance in their voices.This paper proposes an improved genetic algorithm combined with a data enhancement method for Parkinson’s speech signal recognition.Specifically,the methods first extract representative speech signal features through the L1 regularization SVM and then enhance the representative feature data by the SMOTE algorithm.Following this,both original and enhanced features are used to train an SVM classifier for speech signal recognition.An improved genetic algorithm was applied to find the optimal parameters of the SVM.The effectiveness of our proposed model is demonstrated by using Parkinson’s disease audio data set from the UCI machine learning library,and compared with the most advancedmethods,our proposed method has the best performance.

Gene replacement therapy in Bietti crystalline corneoretinal dystrophy:an open-label,single-arm,exploratory trial

Bietti crystalline corneoretinal dystrophy is an inherited retinal disease caused by mutations in CYP4V2,which results in blindness in the working-age population,and there is currently no available treatment.Here,we report the results of the first-in-human clinical trial(NCT04722107)of gene therapy for Bietti crystalline corneoretinal dystrophy,including 12 participants who were followed up for 180-365 days.This open-label,single-arm exploratory trial aimed to assess the safety and efficacy of a recombinant adeno-associated-virus-serotype-2/8 vector encoding the human CYP4V2 protein(rAAV2/8-hCYP4V2).Participants received a single unilateral subretinal injection of 7.5×10^(10)vector genomes of rAAV2/8-hCYP4V2.Overall,73 treatment-emergent adverse events were reported,with the majority(98.6%)being of mild or moderate intensity and considered to be procedure-or corticosteroid-related;no treatment-related serious adverse events or local/systemic immune toxicities were observed.Compared with that measured at baseline,77.8%of the treated eyes showed improvement in best-corrected visual acuity(BCVA)on day 180,with a mean±standard deviation increase of 9.0±10.8 letters in the 9 eyes analyzed(p=0.021).By day 365,80%of the treated eyes showed an increase in BCVA,with a mean increase of 11.0±10.6 letters in the 5 eyes assessed(p=0.125).Importantly,the patients’improvement observed using multifocal electroretinogram,microperimetry,and Visual Function Questionnaire-25 further supported the beneficial effects of the treatment.We conclude that the favorable safety profile and visual improvements identified in this trial encourage the continued development of rAAV2/8-hCYP4V2(named ZVS101e).